|Homo sapiens Gene: DDX58|
|Last Modified||2014-10-13 [Report errors or provide feedback]|
|Gene Name||DEAD (Asp-Glu-Ala-Asp) box polypeptide 58|
|Synonyms||RIG-I; RIGI; RLR-1;|
DEAD (Asp-Glu-Ala-Asp) box polypeptide 58
DEAD (Asp-Glu-Ala-Asp) box polypeptide 58
|Useful resources||Stemformatics EHFPI ImmGen|
DDX58 (RIG-I) is a cytoplasmic RNA helicase that functions as an intracellular sensor of dsRNA leading to the induction of Interferon (IFN) production independently of TLR signalling.
DDX58 (RIG-I) first and second caspase recruitment domains (CARDs) have distinct roles in TRIM25-mediated RIG-I ubiquitination, which leads to initiation of an antiviral signalling cascade.
DDX58 serves as a critical link between TLR3 and type-II-IFN signalling pathways in innate antiviral immune responses.
DDX58 plays an essential role in Toll-like receptor (TLR)-stimulated phagocytosis, demonstrating that DDX58 plays a role not only in antiviral responses but in antibacterial responses as well.
DDX58 plays a key role in the expression of TNF-alpha in macrophages in response to LPS stimulation, mainly for the late phase LPS-induced expression of TNF-alpha.
DDX58 is a sensor able to activate the inflammasome in response to certain RNA viruses by binding to the adaptor PYCARD to trigger the caspase-1 (CASP1)-dependent inflammasome activation and IL-1-beta production.
DDX58 binds specifically to K63-polyubiquitin chains through its tandem caspase recruitment domains (CARDs) that act as a ubiquitin sensor in a manner that depends on RNA and ATP, demonstrate that un-anchored K63-polyubiquitin chains are signalling molecules in antiviral innate immunity.
DDX58 (RIG-I) phosphorylation on serine 8 operates as a negative switch of RIG-I activation by suppressing TRIM25 interaction.
DDX58 innate immune response to viral infection of human cells is modified by a functional polymorphism in the RIG-I caspase recruitment domain (CARD).
DDX58 (RIG-I) is responsible for the cytosolic recognition of Legionella pneumophila RNA and the subsequent induction of type I IFN response. (Demonstrated in murine model)
DDX58 and NOD2 colocalize to cellular ruffles and cell-cell junctions to form a protein complex via the CARD domains. DDX58 negatively regulates ligand-induced NFkB signalling mediated by NOD2, and conversely, NOD2 negatively regulates type I interferon induction by DDX58.
DDX58, through the TRAIL pathway, initiates apoptosis in hepatocytes infected with hepatitis C Virus to suppress viral replication. HCV envelope proteins counteract the antiviral host defence by inhibiting the expression of DDX58.
DDX58 (RIG-I) ubiquitination is inhibited by arterivirus and nairovirus deubiquitinating enzymes (DUBs), resulting in the inhibition of RIG-I-like receptor (RLR)-mediated innate immune signalling. (Demonstrated in mice)
Antiviral stress granules containing DDX58 (RIG-I) and EIF2AK2 (PKR) have a critical role in viral detection and innate immunity. (Demonstrated in mouse)
DDX58 (RIG-I) stimulation with a synthetic ligand inhibits HIV replication in macrophages.
RNF135 is essential for the association of DDX58 (RIG-I) and TRIM25, resulting in the activation of RIG-I signalling.
ISG15 does not directly alter human rhinovirus replication but modulates immune signalling via the viral sensor protein DDX58 to impact production of CXCL10, which has been linked to innate immunity to viruses.
Human rhinovirus infection of epithelial cells induces the expression and secretion of ISG15, which modulates immune responses via effects on DDX58, and by regulating CXCL10 production.
The antisense L region of encephalomyocarditis virus associates with DDX58 and is a key determinant of IFIH1 stimulation of infected cells.
IFI16 transcriptionally regulates type I interferons and DDX58 (RIG-I) and controls the interferon response to both DNA and RNA viruses.
Paramyxoviruses trigger the DNA-damage response, a pathway required for RPS6KA5 activation of phospho Ser 276 RELA formation to trigger the IRF7-DDX58 amplification loop necessary for mucosal interferon production.
DDX58 dually functions as an hepatitis B virus sensor activating innate signalling and as a direct antiviral factor by counteracting the viral polymerase in hepatocytes.
DDX58 is the primary pattern recognition receptor (PRR) for influenza A virus (IAV), but IFIH1 is a significant contributor to the cellular defense against IAV.
Signalling through both DDX58 and TLR3 is important for interferon induction by influenza A virus in alveolar epithelial cells.
Hepatitis B virus-induced MIR146A attenuates cell-intrinsic anti-viral innate immunity through targeting DDX58 and IFIT3.
MIR485 exhibits bispecificity, targeting DDX58 in cells with a low abundance of H5N1 virus and viral PB1 in cells with increased amounts of the H5N1 virus.
A defective interfering RNA isolated from the Hu-191 vaccine strain of measles virus is sensed by PRKRA and DDX58 to initiate an innate antiviral response.
ATP binding is required for DDX58 signalling on viral RNA. ATP hydrolysis provides an important function by recycling DDX58 and promoting its dissociation from non-pathogenic RNA.
Influenza B virus induces IRF3 activation and IL29 (IFNL1) gene expression without a requirement for viral protein synthesis or replication and DDX58 is the critical pattern recognition receptor needed for IRF3 activation.
EFTUD2 is a novel innate immune antiviral regulator that restricts hepatitis C virus infection through a DDX58/IFIH1-mediated, JAK-STAT-independent pathway.
MIR136 exhibits potent antiviral activity against H5N1 influenza A virus and acts as an immune agonist of DDX58.
|InnateDB Annotation from Orthologs|
[Mus musculus] Ddx58 (Rig-I) is responsible for the cytosolic recognition of Legionella pneumophila RNA and the subsequent induction of type I IFN response.
[Mus musculus] Ddx58 and Nod2 colocalize to cellular ruffles and cell-cell junctions to form a protein complex via the CARD domains. Ddx58 negatively regulates ligand-induced NFkB signalling mediated by Nod2, and conversely, Nod2 negatively regulates type I interferon induction by Ddx58. (Demonstrated in human)
[Mus musculus] Ddx58, through the TRAIL pathway, initiates apoptosis in hepatocytes infected with hepatitis C Virus. HCV envelope proteins counteract the antiviral host defence by inhibiting the expression of Ddx58. (Demonstrated in human)
[Mus musculus] Ddx58 (RIG-I) ubiquitination is inhibited by arterivirus and nairovirus deubiquitinating enzymes (DUBs), resulting in the inhibition of RIG-I-like receptor (RLR)-mediated innate immune signalling.
[Mus musculus] Antiviral stress granules containing Ddx58 (RIG-I) and Eif2ak2 (PKR) have a critical role in viral detection and innate immunity.
[Mus musculus] DDX58 (RIG-I) detects cytosolic Listeria monocytogenes infections by sensing secreted bacterial nucleic acids.
[Mus musculus] Ddx58 (RIG-I) is a positive regulator of NF-kB signalling via binding to Nfkb1 mRNA.
[Mus musculus] Ddx58 and Ifih1 are essential pattern recognition receptors for protection against West Nile virus infection in vivo.
[Mus musculus] Ddx58 preferentially binds to coding RNA from S. Typhimurium during infection leading to the expression of IFN beta andthis immunostimulatory activity depends on 5â?² triphosphorylation of RNA.
[Mus musculus] Ddx58 is the primary pattern recognition receptor (PRR) for influenza A virus (IAV), but Ifih1 is a significant contributor to the cellular defense against IAV.
[Mus musculus] Ddx58 acts in parallel with Zbp1 in an RNA polymerase III-dependent manner to initiate glial responses to herpes simplex virus-1.
[Mus musculus] Mir485 exhibits bispecificity, targeting Ddx58 in cells with a low abundance of H5N1 virus and viral PB1 in cells with increased amounts of the H5N1 virus.
DEAD box proteins, characterized by the conserved motif Asp-Glu-Ala-Asp (DEAD), are putative RNA helicases which are implicated in a number of cellular processes involving RNA binding and alteration of RNA secondary structure. This gene encodes a protein containing RNA helicase-DEAD box protein motifs and a caspase recruitment domain (CARD). It is involved in viral double-stranded (ds) RNA recognition and the regulation of immune response. [provided by RefSeq, Jul 2008]
|Genomic Location||Chromosome 9:32455705-32526324|
|Number of Interactions||
This gene and/or its encoded proteins are associated with 119 experimentally validated interaction(s) in this database.
They are also associated with 19 interaction(s) predicted by orthology.
Antiviral mechanism by IFN-stimulated genes pathway
Cytokine Signaling in Immune system pathway
Innate Immune System pathway
TRAF6 mediated IRF7 activation pathway
TRAF6 mediated NF-kB activation pathway
RIG-I/MDA5 mediated induction of IFN-alpha/beta pathways pathway
Interferon Signaling pathway
NF-kB activation through FADD/RIP-1 pathway mediated by caspase-8 and -10 pathway
Immune System pathway
TRAF3-dependent IRF activation pathway pathway
ISG15 antiviral mechanism pathway
Negative regulators of RIG-I/MDA5 signaling pathway
RIG-I-like receptor signaling pathway pathway
Cytosolic DNA-sensing pathway pathway
Hepatitis C pathway
|UniProt Splice Variant|
|RNA Seq Atlas|